Eicosanoids play a fundamental role in the regulation of myometrial contractions. While some eicosanoids stimulate uterine contractions, others can inhibit them. The complex interplay between these two groups of eicosanoids is a likely determinant of the tone of the uterus. Receptor binding is a prerequisite for eicosanoids action, but whether these receptors are also present in pregnant myometrium and whether they change during pregnancy and labor has not been investigated. Eicosanoid action require not only their receptors but also their production. Both of these may very well be regulated by other hormones present during pregnancy. Finally, the mechanism(s) of eicosanoids action after receptor binding are unclear. Using the combination of biochemical, molecular and cell biological techniques, we will investigate myometrial changes of PGF, PGF2 alpha, PGI2 and LTC4 receptors, cyclooxygenase, 5-lipoxygenase, PGE2, PGI2 isomerases and PGF2 alpha synthase during pregnancy, preterm and term labor. In addition, regulation of pregnant human myometrial eicosanoid synthesizing enzymes, eicosanoids production and eicosanoid receptors by hormones present during pregnancy and the mechanism(s) of eicosanoids actions will also be investigated. Virtually none of the aspects of eicosanoids productions and binding discussed in this proposal have been studied in the pregnant human myometrium. The data is expected to advance our knowledge of the role and mechanism(s) of eicosanoids actions which should help to better understand mechanism(s) of initiation of labor at term and preterm. Better understanding can suggest more effective methods of delaying preterm labor and elective induction of labor at term. The delay or prevention of preterm labor can potentially save a large segment of the health care dollars now used for intensive neonatal care.